The novel is set in two different time periods: modern Britain, when George Poole finds that he has a previously unknown sister and follows a trail to a mysterious and ancient organisation in Rome (Puissant Order of Holy Mary Queen of Virgins); and the time of Regina, a girl growing up during the ending of Roman rule in Britain, around AD 400.
The book consists of four distinct parts. The primary purpose of part one is the introduction of the characters, in ancient Britain and the present. Part two introduces a modern first-person view of the Order in Rome while following Regina's budding legacy centuries before. Part three hosts the clash and resolution of Poole and the Order's realities. Part four is a look eons into Humanity's Expansion into the Universe and provides a conclusion in George Poole's present.
Poole leaves England to visit his sister Gina in Florida for information, despite their strained relationship. After spoiling his clever nephews as well as clashing with his distant sister Gina, Poole extracts the contact of a Jesuit priest in Rome and his own retired uncle in Florida. Poole learns from his uncle, Lou Casella, that his twin sister was given to the ancient Order when Poole's parents were unexpectedly landed with twins.
Regina seeks refuge with her servant Cartumandua's relatives in Verulamium but is betrayed by Regina's boyfriend Amator who rapes and abandons her. Verulamium burns down, forcing Regina and Cartumandua's family to live off the land in poverty for over sixteen years. Regina kills a roaming Saxon who nearly rapes her daughter, Brica. This event convinces Regina, the leader of their hamlet, to accept the invitation of warlord Artorius to help restore order to Britain again.
Upon arriving in Rome, Regina contacts Amator, now openly homosexual and a wealthy bakery owner, and demands recompense for abandoning her and her family. Regina re-establishes contact with her mother, Julia, after a cool reunion. Regina joins the Puissant Order of Holy Mary Queen of Virgins, a Christian-adapted faction of the Vestal Virgins located on the Appian Way — an organisation that her family has become intimate with. Regina's leadership revives the ageing Order by converting it into a successful private school. Years later, on the night following her daughter's marriage, the Sack of Rome in 455 by the Vandals occurs. Regina's foresight saves the Order when the women and children are evacuated into the underground Catacombs she had had dug for a sanctuary.
In Regina's twilight years, she establishes important rules precedents for the Order. Unnecessary and unsupportable births are prohibited. A handful of mothers must dedicate their lives to replenishing the Order with births. Before her death in 476 AD, Regina establishes three main rules to govern the Order:
George Poole convinces his Jesuit priest contact to grant Peter access to ancient Catholic records. George's patriarchal roots are traced to a British surveyor named George Poole who came to Rome in 1863. George returns to the Crypt looking for information and finds himself smothered with the familiar smell and contact of those in the Crypt, all of whom share his similar facial features (namely, cloudy grey eyes). His sister Rosa almost persuades him to become assimilated into the Order as a stud but an urgent text message by Peter brings him to his senses.
Peter has a theory explaining the strange peculiarities of the Order. The Order is a family of eusocial humans that evolved from the intense pressures to survive the various conquerings of Rome over the centuries. He cites naked mole rats as an example of eusocial behaviour in mammals. He explains how Regina's three rules result in a "genetic mandate for eusociality." He calls the Order a "human hive" and labels them "Coalescents" — a new kind of human. Peter then suddenly leaves after receiving a text message.
Days later, George learns that Peter has invaded the Crypt and is threatening to set off Semtex plastic explosives in order to expose the Order. Peter and the Slan(t)ers are responsible for the recent bombing of a San Jose research facility investigating quantum gravity technology — under the belief that a higher intelligence would notice the manipulation of space-time and eradicate a possible threat to their superiority. Peter's reasoning in exposing the Crypt is that the Order does not exist for any purpose except for itself. It threatens to destroy humanity as individuals and replace it with mindless drones. Peter Mclachlan then detonates his bombs and dies. George begins the evacuation of the Crypt and the mob of drones emerge hive-like from the crater in the middle of Via Cristoforo Colombo.